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Letrozole concentration is associated with CYP2A6 variation but not with arthralgia in patients with breast cancer.
Borrie, Adrienne E; Rose, Rhiannon V; Choi, Yun-Hee; Perera, Francisco E; Read, Nancy; Sexton, Tracy; Lock, Michael; Vandenberg, Theodore A; Hahn, Karin; Dinniwell, Robert; Younus, Jawaid; Logan, Diane; Potvin, Kylea; Yaremko, Brian; Yu, Edward; Lenehan, John; Welch, Stephen; Tyndale, Rachel F; Teft, Wendy A; Kim, Richard B.
Afiliación
  • Borrie AE; Division of Clinical Pharmacology, Department of Medicine, Western University, London, ON, Canada.
  • Rose RV; Department of Physiology and Pharmacology, Western University, London, ON, Canada.
  • Choi YH; Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.
  • Perera FE; Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.
  • Read N; Department of Oncology, Western University, London, ON, Canada.
  • Sexton T; Department of Oncology, Western University, London, ON, Canada.
  • Lock M; Department of Oncology, Western University, London, ON, Canada.
  • Vandenberg TA; Department of Oncology, Western University, London, ON, Canada.
  • Hahn K; Department of Oncology, Western University, London, ON, Canada.
  • Dinniwell R; Department of Oncology, Western University, London, ON, Canada.
  • Younus J; Department of Oncology, Western University, London, ON, Canada.
  • Logan D; Department of Oncology, Western University, London, ON, Canada.
  • Potvin K; Department of Oncology, Western University, London, ON, Canada.
  • Yaremko B; Department of Oncology, Western University, London, ON, Canada.
  • Yu E; Department of Oncology, Western University, London, ON, Canada.
  • Lenehan J; Department of Oncology, Western University, London, ON, Canada.
  • Welch S; Department of Oncology, Western University, London, ON, Canada.
  • Tyndale RF; Department of Oncology, Western University, London, ON, Canada.
  • Teft WA; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, ON, Canada.
  • Kim RB; Department of Psychiatry, and Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Breast Cancer Res Treat ; 172(2): 371-379, 2018 Nov.
Article en En | MEDLINE | ID: mdl-30094551
PURPOSE: The aromatase inhibitor (AI) letrozole is a first-line drug in the adjuvant treatment of breast cancer in postmenopausal women. Adherence to AI therapy, including letrozole, remains problematic due to the development of debilitating AI-induced arthralgia. Letrozole is metabolized in the liver by CYP2A6. It remains unknown if plasma letrozole levels or CYP2A6 genetic variation is associated with the development of arthralgia. METHODS: We enrolled 126 female breast cancer patients initiated on letrozole therapy and prospectively collected blood samples at baseline and two follow-up time points to determine letrozole plasma concentrations and CYP2A6 genotype. At each visit, participants completed two validated questionnaires to assess the severity of arthralgia symptoms. RESULTS: More than half (55%) of patients experienced a significant increase in their arthralgia symptoms after initiation of treatment. The clinical variables of body mass index (P = 0.0003) and age (P = 0.0430) were negatively and positively associated with plasma letrozole concentrations, respectively. CYP2A6 genotype was significantly associated with letrozole levels (P < 0.0001), and increased plasma letrozole levels were observed in patients with CYP2A6 reduced-function genotypes. Plasma levels of letrozole and CYP2A6 genotype were not significantly associated with a change in pain score from baseline. CONCLUSIONS: CYP2A6 genotype was a significant predictor of letrozole plasma levels, but was not associated with the development of arthralgia.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Artralgia / Citocromo P-450 CYP2A6 Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Revista: Breast Cancer Res Treat Año: 2018 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Artralgia / Citocromo P-450 CYP2A6 Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Revista: Breast Cancer Res Treat Año: 2018 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Países Bajos